4s3f: Difference between revisions
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==IspG in complex with Inhibitor 8 (compound 1077)== | ==IspG in complex with Inhibitor 8 (compound 1077)== | ||
<StructureSection load='4s3f' size='340' side='right' caption='[[4s3f]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4s3f' size='340' side='right'caption='[[4s3f]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4s3f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S3F FirstGlance]. <br> | <table><tr><td colspan='2'>[[4s3f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thet8 Thet8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S3F FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43W:BUT-3-YN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>43W</scene>, <scene name='pdbligand=F3S:FE3-S4+CLUSTER'>F3S</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43W:BUT-3-YN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>43W</scene>, <scene name='pdbligand=F3S:FE3-S4+CLUSTER'>F3S</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g9p|4g9p]], [[2y0f|2y0f]], [[3noy|3noy]], [[4s38|4s38]], [[4s39|4s39]], [[4s3a|4s3a]], [[4s3b|4s3b]], [[4s3c|4s3c]], [[4s3d|4s3d]], [[4s3e|4s3e]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g9p|4g9p]], [[2y0f|2y0f]], [[3noy|3noy]], [[4s38|4s38]], [[4s39|4s39]], [[4s3a|4s3a]], [[4s3b|4s3b]], [[4s3c|4s3c]], [[4s3d|4s3d]], [[4s3e|4s3e]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ispG, TTHA0305 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=300852 THET8])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(E)-4-hydroxy-3-methylbut-2-enyl-diphosphate_synthase (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.7.1 1.17.7.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(E)-4-hydroxy-3-methylbut-2-enyl-diphosphate_synthase (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.7.1 1.17.7.1] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s3f OCA], [http://pdbe.org/4s3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s3f RCSB], [http://www.ebi.ac.uk/pdbsum/4s3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s3f ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s3f OCA], [http://pdbe.org/4s3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s3f RCSB], [http://www.ebi.ac.uk/pdbsum/4s3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s3f ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4s3f" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4s3f" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[IspG|IspG]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Thet8]] | |||
[[Category: Abdel-Azeim, S]] | [[Category: Abdel-Azeim, S]] | ||
[[Category: Bacher, A]] | [[Category: Bacher, A]] | ||
Revision as of 13:37, 1 May 2019
IspG in complex with Inhibitor 8 (compound 1077)IspG in complex with Inhibitor 8 (compound 1077)
Structural highlights
Function[ISPG_THET8] Converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4cPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. Publication Abstract from PubMedIspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Its mechanism of action has been the subject of numerous studies but remained unresolved due to difficulties in identifying distinct reaction intermediates. Using a moderate reducing agent and an epoxide substrate analogue, we were now able to trap and crystallographically characterize various stages in the IspG-catalyzed conversion of 2-C-methyl-d-erythritol-2,4-cyclo-diphosphate into (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate. In addition, the enzyme's structure was determined in complex with several inhibitors. These results, combined with recent electron paramagnetic resonance data, allowed us to deduce a detailed and complete IspG catalytic mechanism, which describes all stages from initial ring opening to formation of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate via discrete radical and carbanion intermediates. The data presented in this article provide a guide for the design of selective drugs against many prokaryotic and eukaryotic pathogens to which the non-mevalonate pathway is essential for survival and virulence. Atomic-Resolution Structures of Discrete Stages on the Reaction Coordinate of the [FeS] Enzyme IspG (GcpE).,Quitterer F, Frank A, Wang K, Rao G, O'Dowd B, Li J, Guerra F, Abdel-Azeim S, Bacher A, Eppinger J, Oldfield E, Groll M J Mol Biol. 2015 Apr 11. pii: S0022-2836(15)00225-9. doi:, 10.1016/j.jmb.2015.04.002. PMID:25868383[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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